Percutaneous Coronary Intervention in Elderly Patients

Abstract

Persons aged 65 years or older, often referred to as the elderly, are a rapidly increasing population in the United States. Cardiovascular disease is the most common cause of morbidity and death in this age group, and acute coronary syndrome accounts for a significant proportion of the deaths. Percutaneous coronary intervention is a well-established treatment for acute coronary syndrome and symptomatic coronary artery disease. However, community studies have shown that elderly patients are less likely to undergo revascularization, perhaps due to a “treatment-risk” paradox: elderly patients—at higher risk of morbidity and death from acute coronary syndrome—are denied revascularization even though they are likely to benefit from it. Age alone is one of the many reasons why percutaneous coronary intervention is avoided in elderly patients. This review examines past clinical trials and the existing evidence that supports performing percutaneous coronary intervention in elderly patients.

Cardiovascular disease is the most common cause of morbidity and death in persons aged 65 years and older, and its incidence increases with age. Older adults are a rapidly increasing population in the United States: by the year 2030, 1 of every 5 individuals might be older than age 65 years.¹ The terms “elderly” and “older adults” usually refer to persons older than 65; however, experts in the field of geriatrics suggest that a more functional definition is necessary to characterize this subgroup of the adult population.² Acute coronary syndrome (ACS) accounts for approximately one third of all deaths in elderly patients in the U.S.,³ and the management of those with coronary artery disease (CAD) poses a challenge because multiple comorbidities might limit treatment options. Unfortunately, there is a paucity of evidence to guide therapy in this population, primarily because advanced age has been an exclusion criterion in most clinical trials.

Percutaneous coronary intervention (PCI), a well-established treatment for ACS and for chronic stable angina refractory to medical therapy, has lowered cardiovascular morbidity and mortality rates in carefully selected patient populations. Community studies have shown that elderly patients are less likely to undergo PCI, mostly because some earlier studies from the pre-stenting period showed lower success rates and increased complication rates in these patients. Furthermore, elderly patients often present with ACS, delay seeking treatment, and have increased rates of atypical symptoms, nondiagnostic electrocardiograms, and multiple comorbidities. Despite these problems, evidence from the medical literature shows that PCI may be a viable treatment option for elderly patients.

Literature Search

The purpose of this clinical review was to examine randomized clinical trials that have evaluated the safety and efficacy of PCI treatment in elderly patients. A PubMed search was performed with use of the terms “elderly,” “older adult,” “percutaneous coronary intervention,” and “percutaneous transluminal coronary angioplasty.” High-quality randomized controlled trials, subgroup analyses of randomized trials, and retrospective studies aimed at evaluating the efficacy of PCI in elderly patients in different clinical situations were included in this review. The citation lists from these publications were also examined for further relevant material. When appropriate, some review articles or websites were included. Finally, since individuals age at varying rates because of differences in physical health, lifestyle, and socioeconomic factors, calendar age is an arbitrary point of reference.² This review defines persons 65 years and older as elderly.

Why is Percutaneous Coronary Intervention Avoided in the Elderly?

For a variety of reasons, the in-hospital mortality rate after PCI tends to be higher in elderly patients than in younger patients. In several trials, advanced age was associated with worse short-term prognosis and higher rates of PCI-related complications.^4–6 Elderly patients are often frail and their CAD extensive, which increases morbidity and mortality rates after PCI. The technical feasibility of performing PCI in elderly patients has been questioned, especially because severe coronary calcification and tortuous vascular anatomy make coronary and vascular approaches difficult. Elderly patients often have multiple comorbidities, including chronic kidney disease, which increases the risks associated with PCI. Physiologic considerations might affect the outcome after PCI, including the prolonged effects of risk factors on the vascular system that lead to more extensive patterns of atherosclerosis in the coronary arteries and other vascular beds; increased vascular stiffness with aging, which leads to systolic hypertension; left ventricular hypertrophy; and decreased left ventricular function. Myocardial diastolic function becomes impaired with aging, and endothelial dysfunction is more prevalent. It is unclear how these physiologic effects of aging relate to the outcome of PCI.

Evidence Supporting Percutaneous Coronary Intervention in Specific Clinical Situations

ST-Elevation Myocardial Infarction

Elderly patients are at high risk when they present with ST-elevation myocardial infarction (STEMI), a condition that often accounts for morbidity and death. Reasons for the high risk include atypical presentation, delays in seeking medical care, health management by noncardiologists, and, frequently, admission to hospitals that have no catheterization facility.^7,8 Elderly patients have been selectively excluded from ACS and revascularization trials because of potentially high mortality rates. Therefore, evidence has been extrapolated from studies of younger patients, which precludes extending the study findings to the population that experiences the most morbidity and death from ACS.^7–9

Primary Angioplasty in Myocardial Infarction-I (PAMI-I) is one of the earlier studies that compared primary PCI to fibrinolytic therapy with tissue plasminogen activator (tPA) in patients with STEMI.¹⁰ A subgroup analysis of this trial showed a trend toward fewer in-hospital deaths and a significant reduction in death or recurrent myocardial infarction (MI) in patients aged ≥65 years who underwent PCI.¹¹ Despite an increased risk of stroke and intracranial hemorrhage in the elderly patients, neither of these events occurred in the PCI group.¹¹ The Global Use of Strategies to Open Occluded Coronary Arteries in Acute Coronary Syndrome (GUSTO IIb) trial showed a strong trend toward lower 30-day mortality rates with PCI than with fibrinolytic therapy in elderly STEMI patients (age ≥70 yr).¹² The Danish Multicenter Randomized Study on Fibrinolytic Therapy versus Acute Coronary Angioplasty in Acute Myocardial Infarction-2 (DANAMI-2) trial¹³ compared STEMI patients transferred for PCI within 2 hours from symptom onset to patients who received on-site tPA. A subgroup of patients aged ≥63 years who underwent PCI had a more significant reduction in 30-day death, MI, or stroke than did the patients who were given tPA.¹³ Smaller trials also showed that in elderly patients (age ≥65 yr) with STEMI, PCI resulted in a significant reduction of death, MI, stroke, or revascularization—proof that primary PCI was superior to tPA in STEMI.^14,15 Further evidence, from the Senior PAMI trial, showed that PCI in elderly patients (age ≥70 yr) who presented with STEMI resulted in a significant reduction in death, MI, or stroke.¹⁶ The Primary Coronary Angioplasty Trial (PCAT) investigators¹⁷ pooled 11 randomized trials of PCI versus fibrinolytic therapy and found a significantly reduced 30-day mortality rate in elderly patients (age ≥70 yr) who underwent PCI, thereby strengthening the evidence favoring PCI in elderly patients with STEMI.¹⁷ The important trials are summarized in Table I. In summary, considerable evidence supports performing PCI in elderly patients who present with STEMI, provided that they are eligible for revascularization.

TABLE I. Trials Supporting PCI in Elderly Patients with STEMI*

Non-ST-Elevation Myocardial Infarction

There has been considerable debate about the optimal therapy for elderly patients who present with unstable angina or non-ST-elevation myocardial infarction (NSTEMI). Opinion is divided between conservative medical therapy and early-invasive treatment because some earlier studies showed either no significant difference between the 2 treatment approaches or an increased risk with invasive treatment (PCI). However, caution must be exercised when interpreting the outcomes of these trials, because they were conducted before stenting became commonplace and before glycoprotein IIb/IIIa inhibitors were available.

The Thrombolysis in Myocardial Infarction (TIMI) IIIB trial¹⁸ is one of the earliest studies to have compared early-invasive treatment (routine cardiac catheterization within 48 hours of ACS presentation) with conservative medical management in patients with unstable angina or NSTEMI. In a subgroup analysis of this trial, patients aged 65 years or older experienced a significant reduction in death or MI after early-invasive treatment.¹⁸ However, this trial was also conducted in the pre-stent period. The Fragmin and Fast Revascularization during Instability in Coronary Artery Disease (FRISC II) trial,¹⁹ a randomized study of invasive versus conservative approaches in NSTEMI patients, was the first to show a significantly reduced rate of death or MI in the invasive arm of the study. A subgroup analysis of this trial showed that elderly patients (age ≥65 yr) had a greater relative and absolute risk reduction in death or MI in comparison with the younger patients.²⁰

The Treat Angina with Aggrastat and Determine Cost of Therapy with an Invasive or Conservative Strategy (TACTICS-TIMI 18) investigators²¹ compared early-invasive and conservative approaches in patients with NSTEMI and concluded that there was a significant reduction in the composite endpoint of death, MI, and rehospitalization in the invasive arm of the study. In a subgroup analysis of this trial,²² elderly patients (age ≥65 yr) had greater absolute and relative risk reductions in death or MI at 30-day follow-up. This trial also showed an increasing benefit of an early-invasive approach with advancing age. Although a later trial²³ that compared early versus routine invasive care in patients with NSTEMI found no significant difference in the outcome between the 2 approaches, a nonsignificant trend in the elderly subgroup (age ≥65 yr) favored early invasive care. This same trend was confirmed in some observational studies in the community population.²⁴ Even though in-hospital mortality rates were higher among elderly patients, the National Cardiovascular Data Registry for outcomes after PCI showed an overall temporal improvement in the adjusted in-hospital mortality rate after PCI. This finding was more significant in the oldest subgroup of patients.²⁵

In summary, elderly patients with NSTEMI seem to benefit from an early-invasive approach, but careful selection of patients on the basis of physicians' clinical judgment is necessary to preserve this benefit. Advanced age alone should not preclude PCI in patients who are otherwise eligible for the procedure.

Cardiogenic Shock

There is conflicting evidence regarding the early-invasive approach in elderly patients who present in cardiogenic shock. The SHOCK trial,²⁶ which examined the usefulness of early revascularization therapy in patients with cardiogenic shock, found a significantly reduced mortality rate in the invasive arm of the study. However, this benefit was seen only in patients younger than 75 years; patients who were 75 or older had worse outcomes after the early-invasive approach. The difference was attributed to small numbers of elderly patients in the study and inequalities in the baseline characteristics of those patients in the invasive arm of the study.²⁶ On the other hand, another registry of patients who underwent PCI for cardiogenic shock showed a marked survival benefit in patients 75 or older who received emergency revascularization.²⁷ Other studies^28,29 have shown a significant benefit of emergency revascularization in terms of decreased mortality rates in carefully selected elderly patients with cardiogenic shock. In summary, there appears to be a definite benefit from early revascularization in carefully selected elderly patients who present with cardiogenic shock.

Elective Percutaneous Coronary Intervention

Elective PCI has been studied in a randomized controlled trial that was dedicated to elderly patients. The Trial of Invasive versus Medical Therapy in Elderly Patients with Chronic Symptomatic Coronary Artery Disease (TIME) trial³⁰ compared PCI with optimal medical therapy in elderly patients (age ≥75 yr) who had chronic symptomatic CAD (angina). After a follow-up period of 6 months, the investigators concluded that patients in the PCI arm of the study had improvements in angina and quality of life and had significant reductions in major adverse cardiac events, primarily due to a decreased need for recurrent admissions with ACS. However, at 1-year follow-up, there was no significant difference in symptoms (angina), quality of life, or death between the 2 treatment groups.³¹ Upon 4-year follow-up, long-term survival was similar between the invasive-treatment and medical-therapy groups, but there was still a significant reduction in major adverse cardiac events among patients in the invasive arm of the study—again, due to fewer rehospitalizations for ACS.³² The benefits of both approaches were maintained in regard to angina relief and improved quality of life. Also, regardless of whether patients had undergone revascularization initially or only after drug therapy had failed, their survival rates were better if revascularization had been performed within the 1st year. Hence, even though this was a relatively small study, it shows that elderly patients should undergo revascularization regardless of their age, if they are eligible for the procedure and are symptomatic despite optimal medical therapy.³²

Concomitant Pharmacologic Treatment

There is a paucity of evidence to support the use of concomitant pharmacologic therapies in elderly patients during the periprocedural period. Most evidence pertains to aspirin use in elderly patients with STEMI, unstable angina, and NSTEMI.³³ The Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) trial³⁴ and the PCI-CURE trial³⁵ both showed that the use of clopidogrel and aspirin in elderly patients with unstable angina or NSTEMI decreased the composite endpoint of death, nonfatal MI, or recurrent revascularization in comparison with placebo, thus supporting the use of clopidogrel in this population. The use of glycoprotein IIb/IIIa inhibitors in elderly patients who undergo PCI is controversial, especially because of the increased risk of major bleeding episodes. However, the Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) investigators³⁶ concluded that, when compared with younger patients, patients ≥65 years had a trend toward benefit in terms of death and MI, thus supporting the use of glycoprotein IIb/IIIa inhibitors in the older patients.

Complications of Percutaneous Coronary Intervention in the Elderly

Advanced age is a universal predictor of death in most cardiovascular diseases and cardiac procedures, including PCI. Age is an independent predictor of death after PCI.³⁷ The presence of significant comorbidities such as renal insufficiency, multiorgan dysfunction, and extensive vascular disease may explain the increased mortality rates in elderly patients. Another severe complication after PCI is bleeding (including intracranial hemorrhage), and age is an independent predictor of major bleeding after PCI.³⁸ Table II summarizes some important complications that have been noted in prominent clinical trials.

TABLE II. Complication Rate after PCI in Elderly Patients

Conclusion

Elderly persons are a rapidly growing segment of the U.S. population and can pose a therapeutic challenge because of specific physiologic and anatomic problems. Elderly patients are typically treated less aggressively than are younger patients, due partly to the increased risk of adverse events and partly to a lack of standard management guidelines. Older patients have been excluded from large randomized trials due to comorbidities and age, rendering it impossible to decide upon an optimal approach in most clinical situations. However, on the basis of current evidence, the decision to perform PCI should not be based on chronological age alone, but rather on each patient's general eligibility for revascularization and the clinical circumstances as a whole.